Epigenetics Review Flashcards

Epigenetics Overview

  • Definition:
    • Epigenetics literally means "on top of genetics."
    • Involves chemical modifications of DNA and histones that alter gene expression without changing the DNA sequence.
    • Governs processes that determine how and when genes are expressed and can be inherited or acquired.

The Epigenome

  • Understanding the Epigenome:
    • Despite all cells containing the same genes, gene expression varies significantly across different cell types (e.g., nerve cells, muscle tissue).
    • The epigenome must be reprogrammed after fertilization, where epigenetic tags are reset to allow embryonic cells to develop into various cell types.
    • Epigenetic memory allows cells to retain their identity and maintain function as they divide.

Gene Regulatory Proteins

  • Function:
    • Proteins that can activate or suppress the expression of genes by adding or removing epigenetic tags.
    • Influence the way DNA is expressed based on internal and environmental signals.

Epigenetic Inheritance

  • Imprinting:
    • Involves the selective silencing of one copy of a gene based on its parental origin.
    • Critical for normal development; unregulated imprinting may lead to genetic disorders such as Prader-Willi and Angelman syndromes.

Environmental Influences on the Epigenome

  • Factors such as diet, stress, and exposure can lead to significant changes in gene expression.
  • Example - The Dutch Hunger Winter:
    • During a famine, malnourished pregnant women produced offspring with lasting effects on obesity and health linked to epigenetic changes.

Nutrition and the Epigenome

  • Dietary choices can influence epigenetic mechanisms with substances that modulate gene expression.
  • Examples of dietary components:
    • Resveratrol (found in red wine) removes acetyl groups from histones, leading to gene expression changes.
    • Sulforaphane from broccoli affects histone acetylation to activate tumor-suppressor genes.

Epigenetics in Behaviour

  • Studies with Rats:
    • Differences in maternal behaviour can result in long-term behavioral changes in offspring, demonstrating epigenetic transmission of traits.
  • Human Implications:
    • Evidence of epigenetic changes in victims of child abuse; epigenetic mechanisms underpinning psychiatric conditions like schizophrenia are being researched.

Mechanisms of Epigenetic Control

  1. DNA Methylation:
    • Addition of methyl groups to cytosine residues, typically at CpG islands, leading to gene silencing.
  2. Histone Modifications:
    • Chemical modifications of histone tails affect chromatin structure and gene accessibility.
  3. Non-coding RNA:
    • RNA molecules that regulate gene expression without coding for proteins.
  4. Chromatin Remodelling:
    • Energy-dependent rearrangement of nucleosomes that influence gene access.

Epigenetic Diseases

  • Various conditions have been linked to epigenetic changes, including:
    • Fragile X Syndrome: Caused by a mutation in the FMR1 gene leading to severe intellectual disabilities.
    • Rett Syndrome: Affects primarily girls, leading to severe developmental delays due to mutations in the MeCP2 gene.

Epigenetic Cancer Research

  • Cancer linked to altered methylation patterns.
    • Hypomethylation: Leads to gene overexpression and chromosomal instability.
    • Hypermethylation: Often silences tumor suppressor genes, enabling uncontrolled growth.
  • Case studies illustrate how identical twins may develop different cancers due to epigenetic changes influenced by environmental factors.

Epigenetic Therapy

  • Research into drugs that can modify gene expression without changing DNA sequences.
  • Methyltransferase inhibitors and deacetylase inhibitors are examples of drugs under investigation for potential therapeutic use.